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Credit: https://www.wired.com/story/long-strange-life-worlds-oldest-naked-mole-rat/

Age-defying naked mole rat may hold the key to longevity in human beings

June 23, 2021

Researchers around the world are leaving no stone unturned in the quest to unlock the secrets to longevity in human beings.
Naked mole rats age abnormally and live up to five times the lifespan of similarly sized rodents.
Multiple labs have conducted experiments to better understand the adaptations that make naked mole rats so long lived and resistant to chronic diseases.

Scientists have turned to naked mole rats as they search for interventions that could help increase human healthspan and lifespan. Aging results in deterioration of cellular function that culminates in chronic illnesses and eventually death. This decline happens due to DNA damage, cellular senescence, inflammation, breakdown of cellular communication, mitochondria dysfunction, and other factors that have been identified as biological hallmarks of aging. The accumulation of damage throughout aging can be depicted by what is referred to as the Gompertz mortality law. This is a mathematical framework that quantifies the exponential increase in the risk of death as an animal gets older. For instance, a lab mouse’s risk of dying doubles every three months. Once a human being reaches the age of 25, the risk of dying doubles after every 8 years. Recent scientific endeavor has explored numerous models that could help reverse the course of this downward curve. One small animal that has crossed researchers’ radar is the naked mole rat. While almost all animals suffer from endless diseases of aging, the naked mole rat enjoys an incredibly long and healthy life. Dr. Rochelle Buffenstein is one of the world’s top authorities on naked mole rats. She is also a leading investigator at Google’s anti-aging laboratory, Calico. In 2018, she published a paper demonstrating how naked mole rats defied the Gompertz mortality law. “It’s not that these fascinating rodents don’t age or get sick. They do, but their bodies somehow slow down those processes. They clearly have a blueprint to stave off aging,” says Dr. Buffenstein. Typical mammals’ bones tend to become more brittle and thinner with aging. The bones of naked mole rats — on the other hand — remain just as solid and maintain their mineral composition. While people tend to add more fat with age, naked mole rats don’t. These are unusual characteristics that have fascinated researchers. But according to Dr. Buffenstein, perhaps the most striking observation is the cardiovascular system. Heart disease is the leading cause of death in the US, claiming over half a million lives each year. Much of this chronic disease can be attributed to an age-associated stiffening of the arteries, which makes it harder for the heart to pump blood, raises the blood pressure, and increases risk of death. Researchers noticed that blood vessels and heart function in naked mole rats stays springy right from an early age to extreme old age. The same can be said for cancer, which is the second leading cause of death in the US An estimated 40% of Americans battle cancer at a point in their lifetime. To the contrary — the precedence of cancer in studied mole rat population was well under 1%. This unexpected resilience means there’s something about the biology of these animals that might (possibly) be transferable to human beings. Researchers have been delving into the cellular biology of this special rodent to try and unearth the secret. Dr. Buffenstein’s work has shown that naked mole rates have up to 10 times of a protein called P53 – which is known to suppress tumors — in their connective tissue compared to humans and mice. Other labs are studying the animal’s gut microbiome or grappling with the idea of reprogramming the mole rat’s stem cells. Levels of NRF2 – a protein that is naturally available in all mammals and appears to protect cells and prevent chronic diseases — also appears to be more active in naked mole rat. NRF2 is already used in numerous medications and is currently in clinical trials to test its efficacy against aging in humans. But scientists are wary about jumping to conclusions and putting drugs and compounds to new uses. Too high or too low can lead to undesired effects, including cancerous growth. “We’ve always got to be careful, because so many disease states have hijacked the same proteins to make them work in their favor, too. It’s that very fine line of figuring out how this will help you, versus how this could be used to kill you,” says Buffenstein. It’s highly unlikely that the naked mole rat gets its longevity from just one gene or enzyme. It may be the end result of multiple adaptations, each working in tandem to keep the body alive. Luckily, biotech tools to decode animal secrets have gotten supercharged in recent years. Genome analysis is now faster and more reliable than ever. There are still questions that need to be answered and drugs may be a long way coming. But any progress that researchers make to further uncover the hidden adaptations of this animal may be a step towards potential human treatments.

References: https://www.wired.com/story/long-strange-life-worlds-oldest-naked-mole-rat/

Age-defying naked mole rat may hold the key to longevity in human beings

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